A number of these compounds and intermediates are [[OSDDMalaria:GSK_Arylpyrrole_Series:available_compounds|available]] for biological testing from Todd group by request.

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A number of these compounds and intermediates are [[OSDDMalaria:GSK_Arylpyrrole_Series:available_compounds|available]] for biological testing from Todd group by request. If you would like to contribute new analogues, please check the list of [[OSDDMalaria:GSK_Arylpyrrole_Series:desired_compounds|desired]] compounds.

Series was [http://pubs.acs.org/doi/abs/10.1021/ml200135p listed as one of the most promising leads] from TCAMS set (though lacking aryl F)<br>

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Series was released in a [http://www.nature.com/nature/journal/v465/n7296/full/nature09107.html large dataset] by GSK and later [http://pubs.acs.org/doi/abs/10.1021/ml200135p listed as one of the most promising leads] from TCAMS set (though lacking aryl F)<br>

==== TCMDC 123812 ====

==== TCMDC 123812 ====

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[[Image:Nearneighbour2.png|thumb|center|450px|Current synthesis of near neighbours]]

[[Image:Nearneighbour2.png|thumb|center|450px|Current synthesis of near neighbours]]

Synthesis method taken from [http://dx.doi.org/10.1016/j.bmcl.2011.09.049 this paper].

Synthesis method taken from [http://dx.doi.org/10.1016/j.bmcl.2011.09.049 this paper].

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=== Alternative side-chains ===

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Some alternative heterocyclic side-chain ideas have been proposed [http://www.thesynapticleap.org/node/367 here] at the Synaptic Leap.

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==== Oxazoles ====

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The [http://en.wikipedia.org/wiki/Oxazole|oxazole] side chain would target ester isosteres (see TCMDC-123812) but with greater biological stability.

According to [http://dx.doi.org/10.1016/j.bmcl.2011.09.049 this paper], similar compounds are agonists of the sphingosine-1-phosphate receptor subtypes 1-5, which have a role in immune system function.

According to [http://dx.doi.org/10.1016/j.bmcl.2011.09.049 this paper], similar compounds are agonists of the sphingosine-1-phosphate receptor subtypes 1-5, which have a role in immune system function.

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A new class of antimalarial was recently published by Novartis, [http://dxd.doi.org/10.1021/jm2003359 Imidazolopiperazines].

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A new class of antimalarial was recently published by Novartis, [http://dx.doi.org/10.1021/jm2003359 Imidazolopiperazines].

* 58 rhodanines. These do not contain any biological data, presumably omitted due to promiscuity/PAINS issues.

'''Scifinder Search:'''

'''Scifinder Search:'''

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[http://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20091112&DB=EPODOC&locale=en_EP&CC=WO&NR=2009137133A2&KC=A2&ND=5 WO 2009137133 (A2)] 5-Substituted-2-Imino-Thiazolidinone Compounds And Their Use As Inhibitors Of Bacterial Infection

[http://worldwide.espacenet.com/publicationDetails/biblio?FT=D&date=20091112&DB=EPODOC&locale=en_EP&CC=WO&NR=2009137133A2&KC=A2&ND=5 WO 2009137133 (A2)] 5-Substituted-2-Imino-Thiazolidinone Compounds And Their Use As Inhibitors Of Bacterial Infection

[[Image:WO2009137133A2.png|thumb|none|Bacterial inhibitor]]

[[Image:WO2009137133A2.png|thumb|none|Bacterial inhibitor]]

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===Synthetic Routes to Analogs Proposed By Others===

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The CRO Asclepia, via Frederik Doroose, contributed these synthetic routes to the project:

sC, sD, sF, sJ, sI: [http://openwetware.org/images/e/ee/Ascelpia_Several.doc Word file]. Note prices are for S/M and should not be taken as a quote value.

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== Biology ==

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=== Malaria Assays ===

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==== '''''In vitro''''' ====

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Current tested compounds and their biological activities are summarised on a Google [http://bit.ly/OSDDcompounds spreadsheet]

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The results are collected on [http://malaria.ourexperiment.org/biological_data malaria.ourexperiment.org].

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==== '''''In vivo''''' ====

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TCMDC-123812, TCMDC-123794 and near neighbour ZYH 3-1 have been [http://www.thesynapticleap.org/node/395 submitted] for study oral ''in vivo'' mouse model. Unfortunately it was found that the compounds possess zero oral efficacy (Results available [http://malaria.ourexperiment.org/uri/ed here]) in this initial trial.

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=== Mode of action ===

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==== ''In silico'' prediction ====

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''In silico'' prediction of targets has been carried out by [https://plus.google.com/u/0/b/114702323662314783325/115238763121035691959/posts Iain Wallace] and summarised by [[User:Matthew_Todd|Mat]] on [http://www.thesynapticleap.org/node/387 the synaptic leap]. Detail on the procedure is given on the [http://malaria.ourexperiment.org/in_silico_prediction/2675 ELN]. The following targets were identified from data derived from the ChEMBL database:

A number of these compounds and intermediates are available for biological testing from Todd group by request. If you would like to contribute new analogues, please check the list of desired compounds.

Biology

Malaria Assays

In vitro

In vivo

TCMDC-123812, TCMDC-123794 and near neighbour ZYH 3-1 have been submitted for study oral in vivo mouse model. Unfortunately it was found that the compounds possess zero oral efficacy (Results available here) in this initial trial.

Mode of action

In silico prediction

In silico prediction of targets has been carried out by Iain Wallace and summarised by Mat on the synaptic leap. Detail on the procedure is given on the ELN. The following targets were identified from data derived from the ChEMBL database: